It has been well documented that cigarette smoking has adverse effects on human health. Cigarette smoking is known to increase the risk of cancer in many different organs, such as lung, larynx, esophagus, bladder, pancreas and cervix. In the mouth, tobacco smoke has been demonstrated to be highly correlated with diminution of salivary secretion, periodontal disease, hyperkeratinization, leukoderma, leukoplakia and cancer of the oral mucosa. Epidermal growth factor (EGF) is a well characterized mitogen of A 53-amino acid peptide which is secreted primarily by the granular convoluted tubule cells of the submandibular glands of mice, rats and man. EGF may plan an important role in maintaining the integrity of the mucosal tissues in the alimentary tract including oral cavity. The binding of EGF to a cell surface receptor is the first step in a chain of reactions that culminates in cell mitosis. Preliminary studies demonstrated the presence of specific EGF receptors in rat buccal mucosal cells as well as human buccal tissue. Recent evidence strongly supports an interaction between polyaromatic hydrocarbon compounds (including cigarette smoke) and growth factor receptors. It is hypothesized that cigarette smoking alters salivary EFG level and impairs the EFG receptor function in oral mucosa. The specific aims of this proposed research are:To study 1) the effect of cigarette smoking on EGF level in human saliva. The correlation between the salivary continine (major metabolite of nicotin) level and salivary EGF level, salivary flow rate or titratable base will be analyzed. 2) the effect of cigarette smoking on the biochemical properties of EGF receptor in human buccal tissue. 3) the effect of cigarette smoking on EGF receptor-mediated cellular responses. 4) the molecular mechanism by which cigarette smoking alters the mRNA level of EGF receptor in buccal tissue. The long-term goal is to investigate whether the malignant effect of cigarette smoking on oral mucosal is associated with the salivary EGF level and/or EGF receptor in buccal tissue. The outcome of this research may help to develop strategies for prevention and treatment of tobacco-induced oral mucosal diseases including cancer.